Pleiotropy of positive selection in ancient ACE2 suggests an alternative hypothesis for bat- specific adaptations to host coronaviruses

• 成果类型: Article
• 署名作者: Guo, Yuan Ting; Jiang, Ji-Bin; Qiao, Guan-Rong; Luo, Rong-Hua; Zhou, Xin; Hua, Rong; Zheng, Chang-Bo; Liu, Zhen
• 署名单位: Northwest University Xi'an; Chinese Academy of Sciences; Kunming Institute of Zoology, CAS; Chinese Academy of Sciences; University of Chinese Academy of Sciences, CAS; Kunming Medical University; Kunming Medical University; Chinese Academy of Sciences; Kunming Institute of Zoology, CAS; Chinese Academy of Sciences; Kunming Institute of Zoology, CAS
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-9103
• DOI: 10.1073/pnas.2321619121
• 发表日期: 2024-06-11
• 关键词: evolution; reveal

摘要

Angiotensin - convertingenzyme 2 (ACE2) has dual functions, regulating cardiovascular physiology and serving as the receptor for coronaviruses. Bats, the only true flying mammals and natural viral reservoirs, have evolved positive alterations in traits related to both functions of ACE2. This suggests significant evolutionary changes in ACE2 during bat evolution. To test this hypothesis, we examine the selection pressure in ACE2 along the ancestral branch of all bats (AncBat - ACE2), where powered flight and bat - coronavirus coevolution occurred, and detect a positive selection signature. To assess the functional effects of positive selection, we resurrect AncBat - ACE2 and its mutant (AncBat - ACE2 - mut) created by replacing the positively selected sites. Compared to AncBat - ACE2 - mut, AncBat - ACE2 exhibits stronger enzymatic activity, enhances mice's performance in exercise fatigue, and shows lower affinity to severe acute respiratory syndrome coronavirus 2 (SARS - CoV - 2). Our findings indicate the functional pleiotropy of positive selection in the ancient ACE2 of bats, providing an alternative hypothesis for the evolutionary origin of bats' defense against coronaviruses.